The human retina is exceedingly thin, yet its 1/100th of an inch thickness supports a vast microcosm of diverse cells organized in discrete layers, each playing a critical role in the visual process. Cell types present in the retina include ganglion, bipolar, horizontal, amacrine, cone and rod photoreceptor, leukocyte, erythrocyte and retinal pigment epithelial cells. Imaging the retina through the natural pupil of the eye is a critical diagnostic tool for evaluating the health of the eye. Since pathogenesis begins at the cellular level, both the clinician and the researcher best interpret abnormal physiology of the retina when they understand and can visualize these changes in the microscopic realm. For the clinician, when microscopic tissue changes correlate with macroscopic disease, the diagnosis is more precise and timely and the treatment is better informed. Such retinal pathologies include macular degeneration, retinitis pigmentosa, glaucoma, and diabetic retinopathy. Yet despite major advances in retinal cameras, less than 0.2% of human retinal cells have been visualized in vivo and the potential benefit of observing these cells has remained untapped. Retinal microscopy is extremely challenging because (1) optical aberrations primarily in the cornea and crystalline lens substantially blur the retinal image and (2) reflections from cells at many different depths in the thick retina are weak and create a host of superimposed images at the detector.
Adaptive optics (AO), a technique that is well established in the field of astronomy to correct blur induced by atmospheric turbulence, has been applied to measuring and correcting the ocular aberrations of the eye. AO relies on a wavefront sensor that measures the wavefront distortion and sends a signal through a computer processor to a wavefront corrector (e.g. deformable mirror or spatial light modulator), which can be adjusted to correct for the distortion. Some basic principles of AO are described in Tyson, R. K., Principles of Adaptive Optics, Academic Press, New York, 1998; and Hardy, J. W., Adaptive Optics for Astronomical Telescopes, Oxford University Press, New York, 1998. Using AO, researchers have been able to routinely observe single cells in the living human retina (see, e.g., Liang et al. J. Opt. Soc. Am. A, 14, 2884-2892, 1997). The experiment was conducted using a special camera equipped with AO, which compensated for the most significant ocular aberrations in the subject's eye and provided the eye with unprecedented image quality. A scientific-grade Charge Coupled Device (CCD) array collected—through the compensated optics—short four millisecond images of a flood-illuminated patch of retina. The short exposures were sufficient to adequately freeze retinal motion and preclude blurring. Correction of the ocular aberrations and reduction of retinal motion enabled sharp images of the retina to be collected with enhanced transverse resolution. This increase in transverse resolution was sufficient to enable single cells, such as cone photoreceptors, to be resolved in subjects with normal optics. The AO camera, however, is limited to viewing high contrast retinal structures, namely cone photoreceptors near the fovea and the retinal vasculature. This limitation is likely due to the camera's inherently poor optical sectioning capability (i.e. poor axial resolution) and the relatively large amount of scatter within the thick retina. The use of AO to produce retinal images is disclosed, for example, in U.S. Pat. Nos. 4,838,679, 5,777,719, 5,949,521, 6,095,651, and 6,379,005.
An imaging technique that provides superior axial resolution (i.e., optical sectioning) is coherence gating, also referred to as optical coherence tomography (OCT). OCT is an interference technique in which low temporal coherence light is split into two light beams, which are reflected from a sample object to be imaged and a reference mirror, respectively. The reflected light is then superimposed to generate an interference pattern that is recorded by a detector. The sample image is derived from the interference pattern. Some basic principles of OCT are described in Huang, D. et al., Science, 254, 1178-1181, 1991; Fercher, A. F., J. Biomed. Opt., 1, 157-173, 1996; and Bouma, B. E. et al., Handbook of Optical Coherence Tomography, 2002. The usefulness of OCT for retinal imaging, however, is limited by significant defocus problems and by blurring that results from the optical aberrations associated with the eye. U.S. Pat. Nos. 5,975,697, 6,095,648, 6,137,585, 6,288,784, 6,293,674, 6,307,634, and 6,325,512, as well as published U.S. Patent Application 2001/0043332 A1, U.S. Patent Application 2001/0000978 A1, and EP 659 383 A2, disclose the use of OCT for imaging the retina.
Despite the availability of the foregoing approaches, there remains a need for an imaging method and apparatus that provides both high transverse resolution and axial resolution in the sample image. The invention provides such a method and apparatus. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.